The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy

IgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) worldwide. The disease course fluctuates, and the most important challenge is the considerable variation in the time lag between diagnosis and the development of a hard clinical end point, such as end-stage kidney disease (ESKD). The reaction of renal tissue to damage resembles the common wound-healing response. One part of this repair in IgAN is the expansion of lymphatic vessels known as lymphangiogenesis. The aim of this work was to establish the prognostic value of the density of lymphatic vessels in the renal biopsy at the time of diagnosis, for predicting the risk of ESKD in a Spanish cohort of patients with IgAN.

We performed a retrospective multicenter study of 76 patients with IgAN. The end point of the study was progression to ESKD. The morphometric analysis of lymphatic vessels was performed on tissue sections stained with antipodoplanin antibody.

Density of lymphatic vessels was significantly higher in patients with IgAN with mesangial hypercellularity >50%, segmental sclerosis, higher degrees of interstitial fibrosis, and tubular atrophy. Patients with more lymphatic vessels had significantly higher values of proteinuria and lower estimated glomerular filtration rate (eGFR). A density of lymphatic vessels ≥8 per mm² was associated with a significantly higher rate of progression to ESKD at 3 years from biopsy. After adjustment for the International IgAN prediction score, at the multivariate logistic regression, high density of lymphatic vessels (≥8 per mm²) remained significantly associated with a higher rate of early progression to ESKD.

This study contributes to the understanding of the natural history of the progression to ESKD in patients with IgAN revealing the density of lymphatics vessels may optimize the prognostic value of the International IgA predicting tool to calculate the risk of ESKD, favoring the evaluation of new targeted therapies.